Comparative analysis of the organelle genomes of Aconitum carmichaelii revealed structural and sequence differences and phylogenetic relationships.

In this study, we conducted an assembly and analysis of the organelle genomes of Aconitum carmichaelii. Our investigation encompassed the examination of organelle genome structures, gene transfer events, and the environmental selection pressures affecting A. carmichaelii. The results revealed distinct evolutionary patterns in the organelle genomes of A. carmichaelii. Especially, the plastome exhibited a more conserved structure but a higher nucleotide substitution rate (NSR), while the mitogenome displayed a more complex structure with a slower NSR. Through homology analysis, we identified several instances of unidirectional protein-coding genes (PCGs) transferring from the plastome to the mitogenome. However, we did not observe any events which genes moved from the mitogenome to the plastome. Additionally, we observed multiple transposable element (TE) fragments in the organelle genomes, with both organelles showing different preferences for the type of nuclear TE insertion. Divergence time estimation suggested that rapid differentiation occurred in Aconitum species approximately 7.96 million years ago (Mya). This divergence might be associated with the reduction in CO2 levels and the significant uplift of the Qinghai-Tibet Plateau (QTP) during the late Miocene. Selection pressure analysis indicated that the dN/dS values of both organelles were less than 1, suggested that organelle PCGs were subject to purification selection. However, we did not detect any positively selected genes (PSGs) in Subg. Aconitum and Subg. Lycoctonum. This observation further supports the idea that stronger negative selection pressure on organelle genes in Aconitum results in a more conserved amino acid sequence. In conclusion, this study contributes to a deeper understanding of organelle evolution in Aconitum species and provides a foundation for future research on the genetic mechanisms underlying the structure and function of the Aconitum plastome and mitogenome.

The genome assembly of Carex breviculmis provides evidence for its phylogenetic localization and environmental adaptation.

Carex breviculmis is a perennial herb with good resistance and is widely used for forage production and turf management. We assembled the genome of 469.01 Mb, revealing 37,372 genes with a BUSCO completeness score of 99.0%. The genome comprises 52.03% repetitive sequences, primarily influenced by recent LTR insertions that have contributed to its expansion. Phylogenetic analysis suggested that C. breviculmis diverged from C. littledalei approximately 6.61 Mya. Investigation into repetitive sequences and expanded gene families (EGFs) highlighted a rapid expansion of tandem duplicate (TD) genes, particularly in areas related to sugar metabolism, various amino acid synthesis, and phenylpropanoid biosynthesis. Additionally, our analysis identified crucial genes involved in secondary metabolic pathways such as glycolysis, phenylpropanoid biosynthesis, and amino acid metabolism, which have undergone positive selection. We reconstructed the sucrose metabolic pathway and identified significant gene expansions, included 16 INV, 9 SPS, and 12 SuSy genes associated with sucrose metabolism, showed varying levels of expansion. In summary, the expansion of these genes, coupled with subsequent positive selection, contributed to C. breviculmis' ability to adapt to environmental stressors. This study lays the foundation for future research on the evolution of Carex plants, their environmental adaptations, and potential genetic breeding.

Comparative Analysis of Chloroplast Genome of Meconopsis (Papaveraceae) Provides Insights into Their Genomic Evolution and Adaptation to High Elevation.

The Meconopsis species are widely distributed in the Qinghai-Tibet Plateau, Himalayas, and Hengduan Mountains in China, and have high medicinal and ornamental value. The high diversity of plant morphology in this genus poses significant challenges for species identification, given their propensity for highland dwelling, which makes it a question worth exploring how they cope with the harsh surroundings. In this study, we recently generated chloroplast (cp) genomes of two Meconopsis species, Meconopsis paniculata (M. paniculata) and M. pinnatifolia, and compared them with those of ten Meconopsis cp genomes to comprehend cp genomic features, their phylogenetic relationships, and what part they might play in plateau adaptation. These cp genomes shared a great deal of similarities in terms of genome size, structure, gene content, GC content, and codon usage patterns. The cp genomes were between 151,864 bp and 154,997 bp in length, and contain 133 predictive genes. Through sequence divergence analysis, we identified three highly variable regions (trnD-psbD, ccsA-ndhD, and ycf1 genes), which could be used as potential markers or DNA barcodes for phylogenetic analysis. Between 22 and 38 SSRs and some long repeat sequences were identified from 12 Meconopsis species. Our phylogenetic analysis confirmed that 12 species of Meconopsis clustered into a monophyletic clade in Papaveraceae, which corroborated their intrageneric relationships. The results indicated that M. pinnatifolia and M. paniculata are sister species in the phylogenetic tree. In addition, the atpA and ycf2 genes were positively selected in high-altitude species. The functions of these two genes might be involved in adaptation to the extreme environment in the cold and low CO2 concentration conditions at the plateau.

Near-Infrared Spectral Characteristic Extraction and Qualitative Analysis Method for Complex Multi-Component Mixtures Based on TRPCA-SVM.

Quality identification of multi-component mixtures is essential for production process control. Artificial sensory evaluation is a conventional quality evaluation method of multi-component mixture, which is easily affected by human subjective factors, and its results are inaccurate and unstable. This study developed a near-infrared (NIR) spectral characteristic extraction method based on a three-dimensional analysis space and establishes a high-accuracy qualitative identification model. First, the Norris derivative filtering algorithm was used in the pre-processing of the NIR spectrum to obtain a smooth main absorption peak. Then, the third-order tensor robust principal component analysis (TRPCA) algorithm was used for characteristic extraction, which effectively reduced the dimensionality of the raw NIR spectral data. Finally, on this basis, a qualitative identification model based on support vector machines (SVM) was constructed, and the classification accuracy reached 98.94%. Therefore, it is possible to develop a non-destructive, rapid qualitative detection system based on NIR spectroscopy to mine the subtle differences between classes and to use low-dimensional characteristic wavebands to detect the quality of complex multi-component mixtures. This method can be a key component of automatic quality control in the production of multi-component products.

Prognostic significance of lymphadenectomyin malignant ovarian sex cord stromal tumor: A retrospective cohort study and meta-analysis.

OBJECTIVES: To evaluate the prognostic significance of lymphadenectomy in malignant ovarian sex cord stromal tumor (SCST). METHODS: The medical records of patients with malignant ovarian SCST who underwent primary surgery from April 2005 to December 2016 were retrospectively reviewed in the Department of Obstetrics and Gynecology of Qilu Hospital. A meta-analysis was performed by searching the PubMed and Embase database up to July 20, 2017. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by STATA statistical software version 19.0. RESULTS: Seventy-two patients with malignant SCST were identified in our institution. The mean age of the patients was 44.3years (range, 8-80years). Among the 72 patients, 69.4% had granulosa cell tumors (GCTs, n=50); 47.2% (n=34) underwent lymphadenectomy, and 52.8% (n=38) did not undergo the surgery. None of the lymph nodes had pathologically confirmed metastasis. No significant differences in overall survival of the patients with SCST or GCT were noted based on patient age, tumor size, surgery extent, or administration of cytotoxic chemotherapy, except tumor stage (P=0.010 in SCTs and 0.029 in GCTs, respectively). Lymphadenectomy showed no statistically significant difference in overall survival of patients with SCST or GCT (P=0.734 and 0.079, respectively). In our meta-analysis, a total of 179 studies were identified through a search strategy, and 13 studies were included eventually; 3223 cases were identified, including those from our institution. The random-effects model was used because of moderate heterogeneity (I2=43.8%, P=0.040). The estimated pooled OR was 0.87 (95% CI, 0.57-1.31), indicating that lymphadenectomy has no statistical significance in improving overall survival in SCSTs (Z=0.68, P=0.496). CONCLUSIONS: Tumor stage is the most important prognostic factor affecting SCST overall survival. There is no significant effect of lymphadenectomy in improving the overall survival of SCSTs. Lymphadenectomy is not recommended in initial staging surgery of SCST due to the extremely low lymph node metastasis rate.

Novel histone deacetylase inhibitors derived from Magnolia officinalis significantly enhance TRAIL-induced apoptosis in non-small cell lung cancer.

Histone modifications play critical roles in the progression of non-small cell lung cancer (NSCLC), which accounts for almost 85% of all diagnosed lung cancers. Magnolol and polyphenol mixture (PM) derived from Magnolia officinalis exhibited remarkable antitumor activities in lung cancer. However, the epigenetic effects and molecular mechanisms of magnolol and PM in NSCLC have yet to be reported. In this study, the epigenetic effects of magnolol and PM in NSCLC were examined in vitro and in vivo. Results revealed that magnolol and PM significantly suppressed the expression levels and function of class I histone deacetylases (HDACs). In A549 and H1299 cells, magnolol and PM remarkably induced cell apoptosis by arresting the cell cycle in the G0/G1 phase while simultaneously activating various pro-apoptotic signals, including TRAIL-R2 (DR5), Bax, caspase 3, cleaved caspase 3, and cleaved PARP. However, these apoptosis-promoting effects could be attenuated by TSA, which is a specific class I HDACs inhibitor. ChIP assays also demonstrated that magnolol and PM significantly enriched the histone acetyl mark (H3K27ac) in the promoter region of DR5. In A549 xenograft model, magnolol and PM notably reduced tumor growth by 44.40% and 35.40%, respectively. Therefore, magnolol and PM, as potential inhibitors of class I HDACs, induced tumor cell apoptosis and suppressed tumor growth partially by epigenetically activating DR5, which is a key protein in death receptor signaling pathway.

Species- and gender-dependent differences in the glucuronidation of a flavonoid glucoside and its aglycone determined using expressed UGT enzymes and microsomes.

Flavonoids occur naturally as glucosides and aglycones. Their common phenolic hydroxyl groups may trigger extensive UDP-glucuronosyltransferase (UGT)- catalysed metabolism. Unlike aglycones, glucosides contain glucose moieties. However, the influence of these glucose moieties on glucuronidation of glucosides and aglycones remains unclear. In this study, the flavonoid glucoside tilianin and its aglycone acacetin were used as model compounds. The glucuronidation characteristics and enzyme kinetics of tilianin and acacetin were compared using human UGT isoforms, liver microsomes and intestinal microsomes obtained from different animal species. Tilianin and acacetin were metabolized into different glucuronides, with UGT1A8 produced as the main isoform. Assessment of enzyme kinetics in UGT1A8, human liver microsomes and human intestinal microsomes revealed that compared with tilianin, acacetin displayed lower Km (0.6-, 0.7- and 0.6-fold, respectively), higher Vmax (20-, 60- and 230-fold, respectively) and higher clearance (30-, 80- and 300-fold, respectively). Furthermore, glucuronidation of acacetin and tilianin showed significant species- and gender-dependent differences. In conclusion, glucuronidation of flavonoid aglycones is faster than that of glucosides in the intestine and the liver. Understanding the metabolism and species- and gender-dependent differences between glucosides and aglycones is crucial for the development of drugs from flavonoids.

Anti-lung Cancer Effects of Polyphyllin VI and VII Potentially Correlate with Apoptosis In Vitro and In Vivo.

Polyphyllin VI (PVI) and polyphyllin VII (PVII) derived from Paris polyphylla possess anti-cancer activities. However, the mechanisms for the anti-lung cancer effects of PVI and PVII remain poorly understood. In this study, PVI and PVII exhibited inhibitory effects on the proliferation of A549 and NCI-H1299 cells. PVI and PVII induced G2/M cell cycle arrest and triggered apoptosis. PVI and PVII upregulated the tumor suppressor protein p53 and downregulated cyclin B1. The two treatments significantly increased the expression levels of death receptor 3, death receptor 5, Fas, cleaved PARP, and cleaved caspase-3. Furthermore, PVI and PVII significantly inhibited the growth of A549 cells in vivo. The tumor inhibitory rates of PVI were 25.74%, 34.62%, and 40.43% at 2, 3, and 4 mg/kg, respectively, and those of PVII were 25.63%, 41.71%, and 40.41% at 1, 2, and 3 mg/kg, respectively. Finally, PVI and PVII regulated the expression of proteins related to the apoptotic pathway in A549 xenografts. In summary, PVI and PVII exhibited strong inhibitory effects on lung cancer cell growth in vitro and in vivo by inducing G2/M cell cycle arrest and triggering apoptosis.

Pinelliae rhizoma, a toxic chinese herb, can significantly inhibit CYP3A activity in rats.

Raw Pinelliae Rhizoma (RPR) is a representative toxic herb that is widely used for eliminating phlegm or treating cough and vomiting. Given its irritant toxicity, its processed products, including Pinelliae Rhizoma Praeparatum (PRP) and Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRPZA), are more commonly applied and administered concomitantly with other chemical drugs, such as cough medications. This study aimed to investigate the effects of RPR, PRP, and PRPZA on CYP3A activity. Testosterone (Tes) and buspirone (BP) were used as specific probe substrates ex vivo and in vivo, respectively. CYP3A activity was determined by the metabolite formation ratios from the substrates. Ex vivo results show that the metabolite formation ratios from Tes significantly decreased, indicating that RPR, PRP, and PRPZA could inhibit CYP3A activity in rats. CYP3A protein and mRNA levels were determined to explore the underlying mechanism. These levels showed marked and consistent down-regulation with CYP3A activity. A significant decrease in metabolite formation ratios from BP was also found in PRPZA group in vivo, implying that PRPZA could inhibit CYP3A activity. Conclusively, co-administration of PR with other CYP3A-metabolizing drugs may cause drug-drug interactions. Clinical use of PR-related formulae should be monitored carefully to avoid adverse interactions.

MiR-205 inhibits cell apoptosis by targeting phosphatase and tensin homolog deleted on chromosome ten in endometrial cancer Ishikawa cells.

BACKGROUND: MicroRNAs (miRNAs) are frequently dysregulated in human cancers and can act as either potent oncogenes or tumor suppressor genes. In the present study, we intend to prove that the gene PTEN (phosphatase and tensin homolog deleted on chromosome ten) is a target gene of miR-205 and to investigate the suppressive effects on PTEN transcriptional activity by enhancing miR-205 expression in endometrial cancer Ishikawa cells. METHODS: Using Ishikawa cells as model systems, we up-regulated miR-205 expression by transient transfection with miR-205 mimics. A luciferase reporter assay, qRT-PCR and western blotting assays were used to verify whether PTEN is a direct target of miR-205. Meanwhile, the modulatory role of miR-205 in the AKT (protein kinase B) pathway was evaluated by determining the AKT phosphorylation. As a biological counterpart, we investigated cell apoptosis using flow cytometry. RESULTS: Our data indicate that miR-205 down-regulates the expression of PTEN through direct interaction with the putative binding site in the 3'-untranslated region (3'-UTR) of PTEN. Moreover, we documented the functional interactions of miR-205 and PTEN, which have a downstream effect on the regulation of the AKT pathway, explaining, at least in part, the inhibitory effects on Ishikawa cell apoptosis of enhancing miR-205 expression. CONCLUSIONS: For the first time, we demonstrate that the expression of PTEN is directly regulated by miR-205 in endometrial cancer cells and leads the inhibition of cellular apoptosis. This relationship could be targeted for new therapeutic strategies for endometrial cancer.

Influence of Eggshell Powder on the Properties of Cement-Based Materials.

Replacing cement with industrial by-products is an important way to achieve carbon neutrality in the cement industry. The purpose of this study is to evaluate the effect of eggshell powder on cement hydration properties, and to evaluate its feasibility as a substitute for cement. The substitution rates of eggshell powder are 0%, 7.5%, and 15%. Studying the heat of hydration and macroscopic properties can yield the following results. First: The cumulative heat of hydration based on each gram of cementitious material falls as the eggshell powder content rises. This is a result of the eggshell powder's diluting action. However, the cumulative heat of hydration per gram of cement rises due to the nucleation effect of the eggshell powder. Second: The compressive strengths of ES0, ES7.5, and ES15 samples at 28 days of age are 54.8, 43.4, and 35.5 MPa, respectively. Eggshell powder has a greater negative impact on the compressive strength. The effect of eggshell powder on the speed and intensity of ultrasonic waves has a similar trend. Third: As the eggshell powder content increases, the resistivity gradually decreases. In addition, we also characterize the microscopic properties of the slurry with added eggshell powder. X-ray Diffraction (XRD) shows that, as the age increases from 1 day to 28 days, hemicaboaluminate transforms into monocaboaluminate. As the content of the eggshell powder increases, FTIR analysis finds a slight decrease in the content of CSH. Similarly, thermogravimetric (TG) results also show a decrease in the production of calcium hydroxide. Although the additional nucleation effect of eggshell powder promotes cement hydration and generates more portlandite, it cannot offset the loss of portlandite caused by the decrease in cement. Last: A numerical hydration model is presented for cement-eggshell powder binary blends. The parameters of the hydration model are determined based on hydration heat normalized by cement mass. Moreover, the hydration heat until 28 days is calculated using the proposed model. The strength development of all specimens and all test ages can be expressed as an exponential function of hydration heat.

Carbon Peaking and Carbon Neutrality in the Cement-Based Materials.

The cement industry plays a significant role in global carbon emissions, accounting for approximately 8% of global anthropogenic carbon dioxide (CO2) emissions [...].

The Effect of Oyster Shell Powder on the High-Temperature-Properties of Slag-Ceramic Powder-Based Geopolymer.

There is a lack of scientific understanding of adding an oyster shell powder (OSP) to geopolymer concrete. The purpose of this study is: (1) to evaluate the high-temperature resistance of the alkali-activated slag ceramic powder (CP) mixture added with OSP at different temperatures, (2) to address the lack of application of environmentally friendly building materials, and (3) to reduce solid waste of OSP pollution and protect the environment. OSP replaces granulated blast furnace slag (GBFS) and CP at 10% and 20% (based on binder), respectively. The mixture was heated to 400.0, 600.0, and 800.0 °C after curing for 180 days. The results of the experiment are summarized as follows: (1) The thermogravimetric (TG) results indicated that the OSP20 samples produced more CASH gels than the control OSP0. (2) As the temperature increased, the compressive strength and ultrasonic pulse velocity (UPV) both decreased. (3) Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) results reveal that the mixture undergoes a phase transition at 800.0 °C, and compared with the control OSP0, OSP20 undergoes a different phase transition. (4) The size change and appearance image results indicate that the mixture with added OSP inhibits shrinkage, and calcium carbonate decomposes to produce off-white CaO. To sum up, adding OSP can effectively reduce the damage of high temperatures (800.0 °C) on the properties of alkali-activated binders.

hsa-mir-133a-2 promotes the proliferation and invasion of cervical cancer cells by targeting the LAMB3-mediated PI3K/ATK pathway.

OBJECTIVE: Cervical cancer, one of the common types of malignant tumors progressed in women, is on the rise in developing countries. Numerous previous studies have demonstrated that hsa-mir-133a-2 miRNA is abnormally expressed in cervical cancer cells. However, its fundamental mechanism in cervical cancer needs to be further clarified. Our study set out to investigate the effect of hsa-mir-133a-2 on the phenotypes of cervical cancer cells as well as any potential molecular processes involved in the proliferation and invasion of cervical cancer cells. METHODS: The Cancer Genome Atlas-cervical squamous cell carcinoma and endocervical adenocarcinoma(TCGA-CESC) was adopted in order to verify the expression of hsa-mir-133a-2 in cervical cancer tissues and to identify its potential targets. The interaction between Laminin subunit beta-3(LAMB3) and hsa-mir-133a-2 was verified by TargetScan database as well as Luciferase reporter assay. The Cell Counting Kit-8 (CCK8) and transwell methods were utilized to assess the influence of hsa-mir-133a-2 on the proliferation and invasion characteristics of cervical cancer cells. We studied the role that hsa-mir-133a-2 plays in cervical cancer progression through Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis as well as Western Blot (WB) experiment. RESULTS: Down-regulation of hsa-mir-133a-2 was detected in cervical cancer tissues. It directly targeted LAMB3 and negatively regulated LAMB3 expression. The overexpression of hsa-mir-133a-2 has a significant inhibiting effect on cervical cancer cell proliferation and invasion. The overexpression of hsa-mir-133a-2 significantly inhibits the proliferation and invasion of cervical cancer cells. Moreover, the LAMB3 was able to up-regulate the phosphorylation levels of AKT and phosphatidylinositol 3-kinase (PI3K) protein in cervical cancer cells. hsa-mir-133a-2 could also modulate the PI3K/AKT signaling pathway by targeting LAMB3. CONCLUSION: hsa-mir-133a-2 inhibits cervical cancer cell proliferation and invasion by indirectly regulating the PI3K/AKT signaling pathway, providing us with a new clinical treatment strategy for cervical cancer.

Uncovering the effects and molecular mechanism of Astragalus membranaceus (Fisch.) Bunge and its bioactive ingredients formononetin and calycosin against colon cancer: An integrated approach based on network pharmacology analysis coupled with experimental validation and molecular docking.

Colon cancer is a highly malignant cancer with poor prognosis. Astragalus membranaceus (Fisch.) Bunge (Huang Qi in Chinese, HQ), a well-known Chinese herbal medicine and a popular food additive, possesses various biological functions and has been frequently used for clinical treatment of colon cancer. However, the underlying mechanism is not fully understood. Isoflavonoids, including formononetin (FMNT) and calycosin (CS), are the main bioactive ingredients isolated from HQ. Thus, this study aimed to explore the inhibitory effects and mechanism of HQ, FMNT and CS against colon cancer by using network pharmacology coupled with experimental validation and molecular docking. The network pharmacology analysis revealed that FMNT and CS exerted their anticarcinogenic actions against colon cancer by regulating multiple signaling molecules and pathways, including MAPK and PI3K-Akt signaling pathways. The experimental validation data showed that HQ, FMNT and CS significantly suppressed the viability and proliferation, and promoted the apoptosis in colon cancer Caco2 and HT-29 cells. HQ, FMNT and CS also markedly inhibited the migration of Caco2 and HT-29 cells, accompanied by a marked increase in E-cadherin expression, and a notable decrease in N-cadherin and Vimentin expression. In addition, HQ, FMNT and CS strikingly decreased the expression of ERK1/2 phosphorylation (p-ERK1/2) without marked change in total ERK1/2 expression. They also slightly downregulated the p-Akt expression without significant alteration in total Akt expression. Pearson correlation analysis showed a significant positive correlation between the inactivation of ERK1/2 signaling pathway and the HQ, FMNT and CS-induced suppression of colon cancer. The molecular docking results indicated that FMNT and CS had a strong binding affinity for the key molecules of ERK1/2 signaling pathway. Conclusively, HQ, FMNT and CS exerted good therapeutic effects against colon cancer by mainly inhibiting the ERK1/2 signaling pathway, suggesting that HQ, FMNT and CS could be useful supplements that may enhance chemotherapeutic outcomes and benefit colon cancer patients.

Luteolin exhibits synergistic therapeutic efficacy with erastin to induce ferroptosis in colon cancer cells through the HIC1-mediated inhibition of GPX4 expression.

Colon cancer continues to be a prevalent gastrointestinal malignancy with a bleak prognosis. The induction of ferroptosis, a new form of regulated cell death, has emerged as a potentially effective strategy for the treatment of colon cancer. However, numerous colon cancer cells display resistance to ferroptosis induced by erastin, a well-established ferroptosis inducer. Finding drugs that can enhance the susceptibility of colon cancer cells to erastin is of utmost importance. This study aimed to examine the synergistic therapeutic impact of combining erastin with a bioactive flavonoid compound luteolin on the ferroptosis-mediated suppression of colon cancer. Human colon cancer HCT116 and SW480 cells were used for the in vitro studies and a xenograft of colon cancer model in BALB/c nude mice was established for the in vivo experiments. The results showed that combinative treatment of luteolin and erastin effectively inhibited the viability and proliferation of colon cancer cells. Luteolin and erastin cotreatment synergistically induced ferroptosis, concomitant with a reduction in glutathione and an elevation in lipid peroxides. In vivo, combinative treatment of luteolin and erastin exhibited a pronounced therapeutic effect on xenografts of colon cancer, characterized by a significant induction of ferroptosis. Mechanistically, luteolin in combination with erastin synergistically reduced the expression of glutathione peroxidase 4 (GPX4), an antioxidase overexpressed in colon cancer cells. Furthermore, luteolin and erastin cotreatment significantly upregulated the expression of hypermethylated in cancer 1 gene (HIC1), a transcriptional repressor also recognized as a tumor suppressor. HIC1 overexpression notably augmented the suppression of GPX4 expression and facilitated ferroptotic cell death. In contrast, HIC1 silencing attenuated the inhibition of GPX4 expression and eliminated the ferroptosis. Conclusively, these results clearly demonstrated that luteolin acts synergistically with erastin and renders colon cancer cells vulnerable to ferroptosis through the HIC1-mediated inhibition of GPX4 expression, which may act as a promising therapeutic strategy.

Cesarean Scar Ectopic Pregnancy Clinical Classification System With Recommended Surgical Strategy.

OBJECTIVE: To establish a new cesarean scar ectopic pregnancy clinical classification system with recommended individual surgical strategy and to evaluate its clinical efficacy in treatment of cesarean scar ectopic pregnancy. METHODS: This retrospective cohort study included patients with cesarean scar ectopic pregnancy in Qilu Hospital in Shandong, China. From 2008 to 2015, patients with cesarean scar ectopic pregnancy were included to determine risk factors for intraoperative hemorrhage during cesarean scar ectopic pregnancy treatment. Univariable analysis and multivariable logistic regression analyses were used to explore the independent risk factors for hemorrhage (300 mL or greater) during a cesarean scar ectopic pregnancy surgical procedure. The model was internally validated with a separate cohort. Receiver operating characteristic curve methodology was used to identify optimal thresholds for the identified risk factors to further classify cesarean scar ectopic pregnancy risk, and the recommended operative treatment was established for each classification group by expert consensus. A final cohort of patients from 2014 to 2022 were classified according to the new classification system, and the recommended surgical procedure and clinical outcomes were abstracted from the medical record. RESULTS: Overall, 955 patients with first-trimester cesarean scar ectopic pregnancy were included; 273 were used to develop a model to predict intraoperative hemorrhage with cesarean scar ectopic pregnancy, and 118 served as an internal validation group for the model. Anterior myometrium thickness at the scar (adjusted odds ratio [aOR] 0.51, 95% CI 0.36-0.73) and average diameter of the gestational sac or mass (aOR 1.10, 95% CI 1.07-1.14) were independent risk factors for intraoperative hemorrhage of cesarean scar ectopic pregnancy. Five clinical classifications of cesarean scar ectopic pregnancy were established on the basis of the thickness and gestational sac diameter, and the optimal surgical option for each type was recommended by clinical experts. When the classification system was applied to a separate cohort of 564 patients with cesarean scar ectopic pregnancy, the overall success rate of recommended first-line treatment with the new classification grouping was 97.5% (550/564). No patients needed to undergo hysterectomy. Eighty-five percent of patients had a negative serum ß-hCG level within 3 weeks after the surgical procedure; 95.2% of patients resumed their menstrual cycles within 8 weeks. CONCLUSION: Anterior myometrium thickness at the scar and the diameter of the gestational sac were confirmed to be independent risk factors for intraoperative hemorrhage during cesarean scar ectopic pregnancy treatment. A new clinical classification system based on these factors with recommended surgical strategy resulted in high treatment success rates with minimal complications.

Activation of telomerase by seminal plasma in malignant and normal cervical epithelial cells.

Seminal fluids are involved in the development of cervical cancer but the underlying mechanism is unclear. Because cellular transformation requires telomerase activation by expression of the telomerase reverse transcriptase (hTERT) gene, we examined the role of seminal fluids in telomerase activation. Significantly elevated hTERT mRNA and telomerase activity were observed in cervical cell lines (HeLa, SiHa and Caski) treated with seminal plasma. Normal cervical epithelial cells expressed minimal levels of hTERT mRNA and telomerase activity, and seminal plasma substantially enhanced both expression and activity. The hTERT promoter activity was similarly increased in seminal plasma-treated HeLa cells and this effect was closely correlated with increased Sp1 expression and binding to the hTERT promoter. Cyclooxygenase-2 (COX-2) was simultaneously increased in HeLa cells exposed to seminal plasma, and blockade of COX-2 induction abolished seminal plasma stimulation of the hTERT promoter activity, hTERT expression and telomerase activity. Prostaglandin E2 (PGE2) mimics the effect of seminal plasma, stimulating Sp1 expression, enhancing Sp1 occupancy on the hTERT promoter and promoter activity. Moreover, tumour growth was robustly enhanced when HeLa cells together with seminal plasma were injected into nude-mice. Taken together, seminal plasma stimulates COX-2-PGE2-Sp1-dependent hTERT transcription, which provides insights into the putative mechanism underlying telomerase activation in cervical epithelial and cancer cells.

Integrated RNA-sequencing and network pharmacology approach reveals the protection of Yiqi Huoxue formula against idiopathic pulmonary fibrosis by interfering with core transcription factors.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a refractory disease. Therefore, developing effective therapies for IPF is the need of the hour. PURPOSE: Yiqi Huoxue Formula (YQHX) is an herbal formula comprising three herbal medicines: Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma, CR), Panax notoginseng (Burk.) F. H. Chen (Notoginseng Radix Et Rhizoma, NR) and Panax ginseng C. A. Mey. (Ginseng Radix Et Rhizoma, GR). This study aims to determine the anti-pulmonary fibrosis effect of YQHX and explore its mechanism of action. STUDY: Design and Methods: The chemical components in the GR, CR and NR extracts were identified by High Performance Liquid Chromatography. A TGF-ß1-induced myofibroblast cell model was used to test the anti-fibrosis effect of GR, CR, NR and YQHX. RNA-sequencing was used to identify the differentially expressed genes (DEGs) after YQHX treatment. Subsequently, gene enrichment analysis and key transcription factors (TFs) prediction for YQHX-regulated DEGs was performed. The active constituents of GR, CR and NR were obtained from the Traditional Chinese Medicine Database and Analysis Platform. Targets of the active constituents were predicted using the similarity ensemble approach search server and Swiss Target Prediction tool. YQHX-targeted key TFs that transcribed the DEGs were screened out. Then, the effect of YQHX on the bleomycin-induced pulmonary fibrosis mouse model was studied. Finally, one of the predicted TFs, STAT3, was selected to validate the prediction accuracy. RESULTS: Seven, two, and five compounds were identified in the GR, CR, and NR extracts, respectively. YQHX and its constituents-GR, CR and NR-inhibited the expression of fibrotic markers, including α -SMA and fibronectin, indicating that YQHX inhibited TGF-ß1-induced myofibroblast activation. RNA-sequencing identified 291 genes that were up-regulated in the TGF-ß1 group but down-regulated after YQHX treatment. In total, 55 key TFs that transcribed YQHX-regulated targets were predicted. A regulatory network of 24 active ingredients and 232 corresponding targets for YQHX was established. Among YQHX's predicted targets, 20 were TFs. On overlapping YQHX-targeted TFs and DEGs' key TFs, six key TFs, including HIF1A, STAT6, STAT3, PPARA, DDIT3 and AR, were identified as the targets of YQHX. Additionally, YQHX alleviated bleomycin-induced pulmonary fibrosis in a mouse model by inhibiting the phosphorylation of STAT3 in the lungs of pulmonary fibrosis mice. CONCLUSIONS: This study provides pharmacological support for the use of YQHX in the treatment of IPF. The potential mechanism of action of YQHX is speculated to involve the modulation of core TFs and inhibition of pathogenetic gene expressions in IPF.

Ultra-Low-Dose Pre-Metallation Strategy Served for Commercial Metal-Ion Capacitors.

HIGHLIGHTS: Interfacial bonding strategy has been successfully applied to address the high overpotential issue of sacrificial additives, which reduced the decompositon potential of Na2C2O4 from 4.50 to 3.95 V. Ultra-low-dose technique assisted commercial sodium ion capacitor (AC//HC) could deliver a remarkable energy density of 118.2 Wh kg-1 as well as excellent cycle stability. In-depth decomposition mechanism of sacrificial compound and the relative influence after pre-metallation were revealed by advanced in situ and ex situ characterization approaches. Sacrificial pre-metallation strategy could compensate for the irreversible consumption of metal ions and reduce the potential of anode, thereby elevating the cycle performance as well as open-circuit voltage for full metal ion capacitors (MICs). However, suffered from massive-dosage abuse, exorbitant decomposition potential, and side effects of decomposition residue, the wide application of sacrificial approach was restricted. Herein, assisted with density functional theory calculations, strongly coupled interface (M-O-C, M = Li/Na/K) and electron donating group have been put forward to regulate the band gap and highest occupied molecular orbital level of metal oxalate (M2C2O4), reducing polarization phenomenon and Gibbs free energy required for decomposition, which eventually decrease the practical decomposition potential from 4.50 to 3.95 V. Remarkably, full sodium ion capacitors constituted of commercial materials (activated carbon//hard carbon) could deliver a prominent energy density of 118.2 Wh kg-1 as well as excellent cycle stability under an ultra-low dosage pre-sodiation reagent of 15-30 wt% (far less than currently 100 wt%). Noteworthily, decomposition mechanism of sacrificial compound and the relative influence on the system of MICs after pre-metallation were initially revealed by in situ differential electrochemical mass spectrometry, offering in-depth insights for comprehending the function of cathode additives. In addition, this breakthrough has been successfully utilized in high performance lithium/potassium ion capacitors with Li2C2O4/K2C2O4 as pre-metallation reagent, which will convincingly promote the commercialization of MICs.